Mutation:BRCA1

Some interesting mutation examples:

• Cys39Arg
• Lys45Gln
• Gly1706Glu
• Gly1706Ala

Germline mutations in the BRCA1 tumor suppressor gene often result in a very significant increase in susceptibility to breast and ovarian cancers. Although the molecular basis of their effects remains largely obscure, many mutations are known to target the highly conserved C-terminal BRCT repeats that function as a phosphoserine/phosphothreonine-binding module. ^[1]

The most common cause of monogenic disease is a single base DNA variant resulting in an amino acid substitution. A set of structural effects, such as reduction in hydrophobic area, overpacking, backbone strain, and loss of electrostatic interactions, is used to represent the impact of single residue mutations on protein stability. The distinction between disease and non-disease variants, strongly supports the hypothesis that loss of protein stability is a major factor contributing to monogenic disease.^[2]